Current methods for thermal imaging (thermography) map gradients in body temperature, but do not map the detailed morphology of tissue structures. The present invention provides a method that maps vascular structures by selectively heating blood vessels relative to the surrounding tissue. This difference in temperature creates a contrast that allows such vessels to be seen in a thermal image. Surgical procedures that require vascular manipulation, such as aneurysm repair, tumor removal, and vascular malformation correction, would greatly benefit from the ability to visualize blood flow in vessels and their distribution beds during such procedures. To grow and progress, for example, solid tumors develop a complex vascular network. Mapping the morphology and function of tumor blood vessels is a potential biomarker of disease status. Further, accurate mapping of tumor vasculature can help delineate tumor margins during resection. The use of thermal imaging to detect tumor margins has been studied, as increased vascular density is associated with the presence of cancer tumors. The technique of the present invention provides accurate mapping of the locations of increased vascular density, and thus cancer tumor margins, by way of example.
Ultrasound is a common method used to map vessels. Standard ultrasound uses sound waves to penetrate soft tissue and then a probe measures the back-reflected wave from dense tissue (such as bone or muscle) to create an image. Doppler ultrasound uses the Doppler effect to measure and image blood flow. There are several types of Doppler systems, which vary in the way the acquired signal is processed and displayed. Ultrasound imaging is a non-invasive, cost effective imaging technique. However, ultrasound has relatively low resolution when compared to other techniques and requires a trained professional to analyze the captured images. Furthermore, ultrasound can produce real-time images, but uses a probe that must be in contact with the area being imaged. This limits its use in surgical techniques where a continuous real-time imaging of the surgical area is necessary.
Computed Tomography (CT) is also used to map the structure of blood vessels, but cannot be used to measure blood flow. CT scans are a series of X-ray images of the object being imaged. Many cross-sectional images are recorded as a scanner emits a narrow beam of X-rays while moving through an arc around the subject. The computer then assembles these 2D scans into a 3D rendering of the object being studied. The use of a helical path is currently being used to eliminate the gaps between cross-sections in standard simple arc scanners. This helical path allows the scanner to take continuous data and to increase the overall speed of the procedure. The images from these scans have excellent spatial resolution (˜500 μm) and excellent penetration through soft tissues. However, there are significant limitations for use of this technique. Because the penetration depth for X-rays is about the same for all soft tissues, contrast agents are needed to distinguish between different soft tissue types in X-ray images. Many patients have allergic reactions to the intravenous contrast agents used to enhance the CT images. CT scans use ionizing radiation to produce images. X-rays are harmful to living tissue and exposure should be minimized when possible. Real-time CT imaging during a procedure is not possible due to the size and slow scanning speeds of the equipment.
Magnetic resonance imaging (MRI) is another method used to map the structure of blood vessels. Unlike CT scanning, MRI does not use X-rays. An MRI scanner uses a static magnetic field and radio waves to create detailed images of the body. MRI is particularly useful for tissues with many hydrogen nuclei and little density contrast, such as the brain, muscle, connective tissue, and most tumors. An MRI scanner creates a strong magnetic field and the protons in soft tissues become aligned with the direction of this external field. During MRI scans radio transmitters are used to broadcast radio frequency (RF) electromagnetic radiation into the body. These RF waves penetrate deeply into all tissue types because there is little absorption or scattering at these wavelengths. The aligned protons absorb a small amount of the RF signal and this flips the spin of the protons into an excited energy state. After the electromagnetic field is turned off, the spins of the protons become re-aligned with the static magnetic field. During this relaxation, a RF signal is generated. This outgoing RF signal is detected and is sent to a computer, which processes the signals into a 3D image of the area being examined. Protons in different tissues return to their equilibrium state at different rates and this effect is used to create contrast between different types of body tissue. MRI contrast agents alter the relaxation times of atoms within body tissues. MRI contrast agents are used to enhance the appearance of blood vessels, tumors, and inflammation. MRI has a good spatial resolution (<1 mm) and is capable of imaging different tissue types regardless of density. However, MRI cannot be used in real-time during a surgical procedure due to slow imaging speed, size of the equipment, and strong magnetic fields created by the scanner.
Optical coherence tomography (OCT) is a noninvasive, high spatial resolution method for imaging biological tissues. OCT is similar to ultrasound, except instead of sound waves, light is used to collect information about the subject. One type of OCT system uses a Michelson interferometer to create images of the subject. A broadband near-IR source is split into two beams; one focused on the subject and the other is used as a reference beam. The subject beam is used to scan the surface of the object being studied. When the subject beam is reflected off the subject it is passed through the interferometer where it is combined with the reference beam. This produces an interference pattern that is analyzed into an image. Doppler OCT combines standard OCT with laser Doppler flowmetry (LDF). LDF measures the frequency shift of light reflected off tissue structures to probe the speed and direction of the structures. By combining this with OCT, an image with excellent spatial resolution (˜10 μm) and flow information can be created. OCT is limited to an imaging depth of 1 to 2 mm due to the absorption and scattering of the light used to probe the tissue. While OCT produces real time images, the field of view is small and the probe needs to be in close proximity to the patient, which can be obtrusive to the surgical team.
The scientific community is currently exploring new methods for imaging vasculature. One of the methods currently being investigated is optoacoustic, or photoacoustic, imaging. This method uses a train of optical pulses to produce a temperature change in tissue. This temperature change produces an acoustic wave caused by the thermoelastic change. This sound wave is then captured with a probe similar to an ultrasound probe. This technique has high spatial resolution. This method does not yet have the ability to map blood flow because the motion of the blood degrades the spatial resolution of the image. This technique also provides only a small field of view.
Thermal imaging allows the visualization of light in the 8 to 10 μm range of the electromagnetic spectrum. Thermal images are displayed as color maps that show variations in temperature of the objects being imaged. Mid-IR imaging is called thermography in medicine because the images obtained are maps of surface temperature as a function of position. Thermography has been used in medicine since the 1960's. It is an attractive imaging option because it is non-invasive and does not use ionizing radiation. Thermography has been used in such applications as the evaluation and treatment of burns and the diagnosis of superficial vascular disorders. In all of these applications, thermal imaging is used to find areas of tissue that experience an increase or decrease in tissue temperature. This temperature variation is the result of increased or decreased blood flow. The resulting images show temperature gradients across the tissue surface. A current limitation of thermography as a medical imaging tool is that the thermal images do not reveal the detailed structure of tissues.
Thermal imaging is a map of the mid-IR light emitted by tissue, so understanding the nature of this emission is necessary for properly interpreting these images. Thermal imaging of tissue treats the human body as a blackbody radiator. This means the tissue emits electromagnetic radiation at all frequencies according to Planck's Law (Equation 1).
                              I          ⁡                      (                          λ              ,              T                        )                          =                                            2              ⁢                              hc                2                                                    λ              5                                ⁢                      1                                          e                                                      h                    ⁢                                                                                  ⁢                    c                                                        λ                    ⁢                                                                                  ⁢                    k                    ⁢                                                                                  ⁢                    T                                                              -              1                                                          Equation        ⁢                                  ⁢        1            I(λ, T) is the intensity for a given wavelength and temperature, h is Planck's constant, c is the speed of light in a vacuum, λ is the wavelength of the electromagnetic radiation, k is Boltzmann's constant, and T is the temperature of the body in Kelvin.
Blackbody emitters also follow Wien's Displacement Law (Equation 2).
                              λ          max                =                  b          T                                    Equation        ⁢                                  ⁢        2            where b is Wien's displacement constant (2.897×10−8 K·m) and T is the temperature of the body in Kelvin. Wien's law tells us the wavelength at which the blackbody emits the most energy. The human body at normal temperature (37.0° C.±0.5) emits light most strongly around 9.5 μm in the thermal IR. As a blackbody radiator gets hotter, the wavelength of peak emission will shift to shorter wavelengths.
The total energy radiated per unit surface area (irradiance, F) for a blackbody is described by the Stefan-Boltzmann Law (Equation 3).F=σT4  Equation 3where σ is Stefan's Constant with a value of
  5.6704  *      10          -      8        ⁢      J                  sm        2            ⁢              K        4            and T is the blackbody's temperature in Kelvin. The Stefan-Boltzmann law shows that as a blackbody radiator gets hotter, it will become brighter (greater irradiance).
FIG. 1 illustrates the differences between blackbody radiators of different temperatures. One object is at normal body temperature and the other is 100° C. warmer. Notice that the warmer object has a peak at a shorter wavelength and is brighter at all wavelengths.